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Primary prostatic involvement in non-hodgkin lymphoma
PRIMARY PROSTATIC INVOLVEMENT IN NON-HODGKIN LYMPHOMA DHIMANT
R. PATEL, M.D.
GERMAN A. GOMEZ, EDWARD
M.D.
S. HENDERSON,
MARIE GAMARRA,
M.D.
M.D.
From the Departments of Medical Oncology and Pathology, Roswell Park Memorial Institute, Buffalo, New York
ABSTRACTWe report 3 cases of primary extranodal lymphoma of the prostate, an unusual extranodal presentation rarely diagnosed antemortem. Symptoms of prostatism associated with an enlarged hard prostate with pyuria and hematuria in younger patients should suggest the diagnosis. Urine cytologic examination should aid in the diagnosis of this condition.
Involvement of the urinary tract by nonHodgkin lymphoma (NHL) occurs in less than 10 percent of patients and manifests as a primary urologic problem in less than 1 percent of patients. 1-3 NHL has been reported to arise in the bladder of elderly women with a history of recurrent cystitis and in the prostate of younger men.4-e Prostatic involvement in non-Hodgkin lymphoma is rarely diagnosed clinically. These patients have been reported as presenting with obstructive symptoms, abdominal mass, hematuria, or sepsis as a consequence of urinary obstruction.2,7-13 Primary lymphoma of the prostate has been reported rarely. Between 1950 and 1964, the end-results group collected information on 1,467 white patients with primary lymphomas. Only 3 patients had prostate involvement . l4 More recently Bostwick and MannI in a review from three institutions (1935 to 1983) reported 7 cases of primary extranodal lymphoma of the prostate. Since there is considerable difficulty in diagnosing and treating these patients at an early stage, we report the clinical presentation and follow-up of 3 patients diagnosed as primary prostatic lymphoma.
96
Material and Methods All cases of non-Hodgkin lymphoma (NHL), extranodal lymphoma, and cases coded as possible lymphoma, lymphosarcoma, and reticulum sarcoma, seen at Roswell Park Memorial Institute (RPMI) f rom 1971 to 1985 were retrospectively reviewed. Of a total of 1,926 patients, 340 had primary extranodal lymphomas including 3 patients with primary prostate lymphoma. All 3 patients met the criteria for primary lymphoma of the prostate established by King and Cox,16 i.e., (1) presenting symptoms attributable to prostatic enlargement; (2) involvement of prostate predominantly, with or without involvement of adjacent tissue; (3) absence of involvement of other organs within one month of diagnosis. Case Reports Case 1 A thirty-two-year-old man was seen at a local hospital for frequency dysuria, nocturia, and poor urinary stream of several weeks’ duration. Evaluation revealed grade II enlargement for which he underwent transurethral resection of prostate. Patient was first seen at RPM1 two
UROLOGY
i
AUGUST
1988
i
VOLUME
XXXII, NUMBER 2
months later with a diagnosis of small cleaved diffuse lymphoma of the prostate and urosepsis. Serum chemistries were normal, urinalysis revealed pyuria, hematuria, and bacteriuria. Staging included negative results on bone marrow, liver biopsy, and lymphangiogram. Patient received radiation therapy (total 4,400 rad) to the prostate and pelvis. Three months later, however, the patient was admitted with urinary obstruction due to involvement with lymphoma of the urethra, ureter, renal pelvis, and spinal cord compression with CNS involvement. This was partially controlled with radiation therapy. Radiation was followed by chemotherapy with nitrogen mustard and vincristine. Terminally, five months after initial diagnosis pneumonia and urosepsis with Enterococci developed. Autopsy showed tumor involved the prostate, urinary bladder wall, renal pelvis, pelvic lymph nodes, femoral marrow, lung, and dura of pituitary fossa. Case 2 A sixty-eight-year-old man presented with urinary retention. l7 He had a two-year history of prostatism which was managed with antibiotics. One month prior to evaluation for urinary retention he had noticed increasing frequency, nocturia, hesitancy, and post-voiding dribbling. On examination patient had an enlarged prostate; urine cytology was positive for malignant lymphoid cells compatible with large-cell lymphoma. Serum chemistries were normal. Patient underwent retropubic prostatectomy and after staging which included lymphangiogram and biopsy of liver and bone mara diagnosis of Stage IAE row specimens, large-cell lymphoma of prostate and benign prostatic hyperplasia was made. The patient received no further treatment; and except for two episodes of bladder neck contracture (biopsy specimens were negative for lymphoma), patient is alive and well with no evidence of disease thirteen years after diagnosis. Case 3 A forty-one-year-old man presented with an eight-week history of prostatism and hematuria revealed an for several days. Evaluation enlarged indurated prostate; biopsy of the specimen revealed mixed small-cleaved and large noncleaved diffuse lymphoma. Urinalysis revealed hematuria and pyuria. Urine cytology was positive for malignant lymphoid cells.
UROLOGY
/ AUGUST
1988
/ VOLUME
Staging workup which included bone marrow examination, liver biopsies, lymphangiogram, gallium scan, and CT scan of abdomen and pelvis revealed the tumor to be localized to the pelvic cavity involving the anterior wall of the rectum and bladder. Serum chemistries were normal. The patient was treated with combination chemotherapy consisting of methotrexate in intermediate dose followed by cyclophosphamide, vincristine, and prednisonelB and involved field radiation (3,600 rad) without response. Due to progressive disease patient underwent radical cystoprostatectomy at seven months and died of extensive disease ten months after diagnosis. Comment Secondary prostatic involvement with cancer is an incidental finding at autopsy, but it is occasionally found at surgery. Leukemia and lymphoma are the most common neoplasms reported to metastasize to the prostate.3 NHL usually arises in nodal tissue and subsequently spreads to distant and visceral sites.‘* Extranodal tissue may be primarily involved in a significant portion of cases; head and neck and the gastrointestinal tract are the most prevalent sites.14,20,21Malignant tumors of the prostate are usually epithelial in origin; adenocarcinema is the most common. Nonepithelial tumors are rare (< 0.1% of malignant prostate tumors) and have a predilection for the young and old.22,23 Historically, primary extranodal lymphoma has been included in discussion of lower urinary tract sarcomas-lymphosarcoma, reticulum cell sarcoma.24.25 Retrospective reviews of patients’ records have disclosed that the level of premortem clinical detection or suspicion and accurate diagnosis of lower urinary tract lymphomas is much lower than the actual incidence at postmortem examination. We present 3 patients in each of whom the primary site of NHL was within the prostate. Two of these patients were relatively young (32 and 41 years). All three presented with nocturia, hesitancy, and poor stream with no previous history of lower urinary tract infection or instrumentation. All 3 patients had an enlarged hard prostate; pyuria, and hematuria on urinalysis. Urine cytology was positive for lymphoma in 212 patients. Each patient had localized disease and normal serum chemistries at time of diagnosis. The coexistence of benign prostatic hyperplasia with primary lymphoma as observed in Case 2 was reported previously
XxX11, NUMBER 2
97
in the literature. 16.26z7 Malignant lymphoma of the prostate was reported to have a poor prognosis regardless of patient’s age, histology, stage, or treatment regimens of the tumor 15.16.26.28-30 Only 1 of the 13 patients reported by Bostwick and Mann15 was alive and free of disease. On the other hand, the low response rate and poor survival observed may be a reflection of the rarity of the condition. One of the 3 patients in this series is alive and free of disease thirteen years after total prostatectomy alone. This case is unique in the literature, and constitutes a true primary lymphoma of the prostate removed surgically. Our observations indicate that NHL should be considered in the differential diagnosis of prostatism/urinary tract obstruction particularly in young patients (i.e., under 50 years old) who have an enlarged prostate associated with pyuria and hematuria. Urine cytologic examination which has not been reported before, should aid in the early diagnosis of these patients. 666 Elm Street Buffalo, New York 14263 (DR. GOMEZ) References 1. Watson EM, Saucer HR, and Sadugor MG: Manifestations of lymphoblastomas in genitourinary tract, J Uro161: 626 (1949). 2. Weimar G, Culp DA, Loening S, and Narayana A: Urogenital involvement by malignant lymphomas, J Urol125: 230 (1981). 3. Tawfik A, et al: Secondary tumors of the prostate, J Urol 133: 615 (1985). 4. Waller JI, and Schullenberger WA: Lymphosarcoma of the prostate, 1 Urol 62: 480 (1940). 5. Bha&li SK, and Cameron KM: Primary malignant lymohoma of the bladder. Br 1 Uro132: 440 11960). I 6. Heaney JA, DeLelliskA, and Rudders Rk: NHL arising in lower urinary tract, J Urol 25: 479 (1985). 7. Lamm DL, and Kaplan GW: Urological manifestations of Burkitt’s lymphoma, J Urol 112: 402 (1974). 8. Whitmore III WF, Skarin AT, and Rosenthal DS: Urological
98
presentations of non-Hodgkin’s lymphomas, J Urol 128: 953 (1982). 9. Elisei AM, Norgard MJ, Durant JR, and Kelly DR: Unusual manifestations of NHL, Cancer 44: 269 (1979). 10. Doll DC, Weiss RB, and Shah S: Lymphoma of the prostate presenting as benign prostatic hypertrophy, South Med J 71: 1170 (1978). 11. Cos LR, and Rashid HA: Primary non-Hodgkin’s lymphoma of prostate presenting as benign prostatic hyperplasia, Urology 23: 176 (1984). 12. Hales DSM, Cassidy M, Scott R, and Lewi HJE: Immunocytoma of prostate, Urology 22: 438 (1983). 13. Brewer WR, Lan CW, and Bunts RC: Complete bilateral ureteral obstruction from leukemia and lymphoma, J Uro198: 186 (1967). 14.’ Freeman C, Berg JW, and Cutler SJ: Occurrence and prognosis of extranodal lvmnhomas. Cancer 29: 252 (1972). 15. Bostwick DC; and Mann RB: Malignant‘lymphomas involving the prostate, Cancer 56: 2932 (1985). 16. King LS, and Cox TR: Lymphosarcoma of prostate, Am J Path01 27: 801 (1951). 17. Cartagena R, Baumgartner G, Wajsman Z, and Merrin C: Preliminary reticulum cell sarcoma of prostate gland, Urology 5: 815 (1975). 18. Gomez GA, et al: Primary chemotherapy for localized non-Hodgkin’s lymphoma of diffuse histology. Preliminary report of a prospective~study, Arch Intern Med 146: 1785 (1986). _ 19. Rosenbere SA. Diamond HD. laslowitz B. and Craver LF: Lymphosarcomg a review of 1,269 &es, Medicine 40: 31(1961). 20. Rudders RA, Ross ME, and DeLellis RA: Primary extranodal lymphoma: response to treatment and factors influencing prognosis, Cancer 42: 406 (1978). 21. Reddy S, Pellettiere E, Saxena V, and Hendrickson FR: Extranodal non-Hodgkin’s lymphoma, Cancer 46: 1925 (1980). 22. Narayana AS, Lo&ring S, and Weimar GW: Sarcoma of the bladder and nrostate. 1 Urol 119: 72 (1978). 23. Smith BH: and Del&er LP: Sarcoma of the prostate gland, Am J Clin Path01 58: 43 (1972). 24. Richmond J, Sherman RS, Diamond HD, and Craver LF: Renal lesions associated with malignant lymphomas, Am J Med 32: 184 (1962). 25. Fuller LM, et al: Extranodal lymphomas of the stomach and head and neck, in Ford RJ: Hodgkin’s Disease and NonHodgkin’s Lymphoma: New Perspectives in Immunopathology, Diagnosis, and Treatment, Houston, Raven Press, ~0127, 1984, p 341. 26. Dial DL: Lymphosarcoma of the prostate; report of a case, J Uro132: 79 (1934). 27. Mason DG: Primary malignant lymphocytoma of the prostate gland, Arch Path01 16: 803 (1933). 28. Humpel N, Richter-Levin D, and Gersh I: Primary lymphosarcoma of prostate, Urology 9: 461 (1977). 29. Sridhar KN, and Woodhouse CR: Prostatic infiltration in leukaemia and lymphoma, Eur Urol 9: 153 (1983). 30. Lewi HJE, et al: Urinary tract lymphomas, Br J Urol 58: 16 (1986).
UROLOGY
/ AUGUST
1988
i
VOLUME
XXXII,
NUMBER
2
R. PATEL, M.D.
GERMAN A. GOMEZ, EDWARD
M.D.
S. HENDERSON,
MARIE GAMARRA,
M.D.
M.D.
From the Departments of Medical Oncology and Pathology, Roswell Park Memorial Institute, Buffalo, New York
ABSTRACTWe report 3 cases of primary extranodal lymphoma of the prostate, an unusual extranodal presentation rarely diagnosed antemortem. Symptoms of prostatism associated with an enlarged hard prostate with pyuria and hematuria in younger patients should suggest the diagnosis. Urine cytologic examination should aid in the diagnosis of this condition.
Involvement of the urinary tract by nonHodgkin lymphoma (NHL) occurs in less than 10 percent of patients and manifests as a primary urologic problem in less than 1 percent of patients. 1-3 NHL has been reported to arise in the bladder of elderly women with a history of recurrent cystitis and in the prostate of younger men.4-e Prostatic involvement in non-Hodgkin lymphoma is rarely diagnosed clinically. These patients have been reported as presenting with obstructive symptoms, abdominal mass, hematuria, or sepsis as a consequence of urinary obstruction.2,7-13 Primary lymphoma of the prostate has been reported rarely. Between 1950 and 1964, the end-results group collected information on 1,467 white patients with primary lymphomas. Only 3 patients had prostate involvement . l4 More recently Bostwick and MannI in a review from three institutions (1935 to 1983) reported 7 cases of primary extranodal lymphoma of the prostate. Since there is considerable difficulty in diagnosing and treating these patients at an early stage, we report the clinical presentation and follow-up of 3 patients diagnosed as primary prostatic lymphoma.
96
Material and Methods All cases of non-Hodgkin lymphoma (NHL), extranodal lymphoma, and cases coded as possible lymphoma, lymphosarcoma, and reticulum sarcoma, seen at Roswell Park Memorial Institute (RPMI) f rom 1971 to 1985 were retrospectively reviewed. Of a total of 1,926 patients, 340 had primary extranodal lymphomas including 3 patients with primary prostate lymphoma. All 3 patients met the criteria for primary lymphoma of the prostate established by King and Cox,16 i.e., (1) presenting symptoms attributable to prostatic enlargement; (2) involvement of prostate predominantly, with or without involvement of adjacent tissue; (3) absence of involvement of other organs within one month of diagnosis. Case Reports Case 1 A thirty-two-year-old man was seen at a local hospital for frequency dysuria, nocturia, and poor urinary stream of several weeks’ duration. Evaluation revealed grade II enlargement for which he underwent transurethral resection of prostate. Patient was first seen at RPM1 two
UROLOGY
i
AUGUST
1988
i
VOLUME
XXXII, NUMBER 2
months later with a diagnosis of small cleaved diffuse lymphoma of the prostate and urosepsis. Serum chemistries were normal, urinalysis revealed pyuria, hematuria, and bacteriuria. Staging included negative results on bone marrow, liver biopsy, and lymphangiogram. Patient received radiation therapy (total 4,400 rad) to the prostate and pelvis. Three months later, however, the patient was admitted with urinary obstruction due to involvement with lymphoma of the urethra, ureter, renal pelvis, and spinal cord compression with CNS involvement. This was partially controlled with radiation therapy. Radiation was followed by chemotherapy with nitrogen mustard and vincristine. Terminally, five months after initial diagnosis pneumonia and urosepsis with Enterococci developed. Autopsy showed tumor involved the prostate, urinary bladder wall, renal pelvis, pelvic lymph nodes, femoral marrow, lung, and dura of pituitary fossa. Case 2 A sixty-eight-year-old man presented with urinary retention. l7 He had a two-year history of prostatism which was managed with antibiotics. One month prior to evaluation for urinary retention he had noticed increasing frequency, nocturia, hesitancy, and post-voiding dribbling. On examination patient had an enlarged prostate; urine cytology was positive for malignant lymphoid cells compatible with large-cell lymphoma. Serum chemistries were normal. Patient underwent retropubic prostatectomy and after staging which included lymphangiogram and biopsy of liver and bone mara diagnosis of Stage IAE row specimens, large-cell lymphoma of prostate and benign prostatic hyperplasia was made. The patient received no further treatment; and except for two episodes of bladder neck contracture (biopsy specimens were negative for lymphoma), patient is alive and well with no evidence of disease thirteen years after diagnosis. Case 3 A forty-one-year-old man presented with an eight-week history of prostatism and hematuria revealed an for several days. Evaluation enlarged indurated prostate; biopsy of the specimen revealed mixed small-cleaved and large noncleaved diffuse lymphoma. Urinalysis revealed hematuria and pyuria. Urine cytology was positive for malignant lymphoid cells.
UROLOGY
/ AUGUST
1988
/ VOLUME
Staging workup which included bone marrow examination, liver biopsies, lymphangiogram, gallium scan, and CT scan of abdomen and pelvis revealed the tumor to be localized to the pelvic cavity involving the anterior wall of the rectum and bladder. Serum chemistries were normal. The patient was treated with combination chemotherapy consisting of methotrexate in intermediate dose followed by cyclophosphamide, vincristine, and prednisonelB and involved field radiation (3,600 rad) without response. Due to progressive disease patient underwent radical cystoprostatectomy at seven months and died of extensive disease ten months after diagnosis. Comment Secondary prostatic involvement with cancer is an incidental finding at autopsy, but it is occasionally found at surgery. Leukemia and lymphoma are the most common neoplasms reported to metastasize to the prostate.3 NHL usually arises in nodal tissue and subsequently spreads to distant and visceral sites.‘* Extranodal tissue may be primarily involved in a significant portion of cases; head and neck and the gastrointestinal tract are the most prevalent sites.14,20,21Malignant tumors of the prostate are usually epithelial in origin; adenocarcinema is the most common. Nonepithelial tumors are rare (< 0.1% of malignant prostate tumors) and have a predilection for the young and old.22,23 Historically, primary extranodal lymphoma has been included in discussion of lower urinary tract sarcomas-lymphosarcoma, reticulum cell sarcoma.24.25 Retrospective reviews of patients’ records have disclosed that the level of premortem clinical detection or suspicion and accurate diagnosis of lower urinary tract lymphomas is much lower than the actual incidence at postmortem examination. We present 3 patients in each of whom the primary site of NHL was within the prostate. Two of these patients were relatively young (32 and 41 years). All three presented with nocturia, hesitancy, and poor stream with no previous history of lower urinary tract infection or instrumentation. All 3 patients had an enlarged hard prostate; pyuria, and hematuria on urinalysis. Urine cytology was positive for lymphoma in 212 patients. Each patient had localized disease and normal serum chemistries at time of diagnosis. The coexistence of benign prostatic hyperplasia with primary lymphoma as observed in Case 2 was reported previously
XxX11, NUMBER 2
97
in the literature. 16.26z7 Malignant lymphoma of the prostate was reported to have a poor prognosis regardless of patient’s age, histology, stage, or treatment regimens of the tumor 15.16.26.28-30 Only 1 of the 13 patients reported by Bostwick and Mann15 was alive and free of disease. On the other hand, the low response rate and poor survival observed may be a reflection of the rarity of the condition. One of the 3 patients in this series is alive and free of disease thirteen years after total prostatectomy alone. This case is unique in the literature, and constitutes a true primary lymphoma of the prostate removed surgically. Our observations indicate that NHL should be considered in the differential diagnosis of prostatism/urinary tract obstruction particularly in young patients (i.e., under 50 years old) who have an enlarged prostate associated with pyuria and hematuria. Urine cytologic examination which has not been reported before, should aid in the early diagnosis of these patients. 666 Elm Street Buffalo, New York 14263 (DR. GOMEZ) References 1. Watson EM, Saucer HR, and Sadugor MG: Manifestations of lymphoblastomas in genitourinary tract, J Uro161: 626 (1949). 2. Weimar G, Culp DA, Loening S, and Narayana A: Urogenital involvement by malignant lymphomas, J Urol125: 230 (1981). 3. Tawfik A, et al: Secondary tumors of the prostate, J Urol 133: 615 (1985). 4. Waller JI, and Schullenberger WA: Lymphosarcoma of the prostate, 1 Urol 62: 480 (1940). 5. Bha&li SK, and Cameron KM: Primary malignant lymohoma of the bladder. Br 1 Uro132: 440 11960). I 6. Heaney JA, DeLelliskA, and Rudders Rk: NHL arising in lower urinary tract, J Urol 25: 479 (1985). 7. Lamm DL, and Kaplan GW: Urological manifestations of Burkitt’s lymphoma, J Urol 112: 402 (1974). 8. Whitmore III WF, Skarin AT, and Rosenthal DS: Urological
98
presentations of non-Hodgkin’s lymphomas, J Urol 128: 953 (1982). 9. Elisei AM, Norgard MJ, Durant JR, and Kelly DR: Unusual manifestations of NHL, Cancer 44: 269 (1979). 10. Doll DC, Weiss RB, and Shah S: Lymphoma of the prostate presenting as benign prostatic hypertrophy, South Med J 71: 1170 (1978). 11. Cos LR, and Rashid HA: Primary non-Hodgkin’s lymphoma of prostate presenting as benign prostatic hyperplasia, Urology 23: 176 (1984). 12. Hales DSM, Cassidy M, Scott R, and Lewi HJE: Immunocytoma of prostate, Urology 22: 438 (1983). 13. Brewer WR, Lan CW, and Bunts RC: Complete bilateral ureteral obstruction from leukemia and lymphoma, J Uro198: 186 (1967). 14.’ Freeman C, Berg JW, and Cutler SJ: Occurrence and prognosis of extranodal lvmnhomas. Cancer 29: 252 (1972). 15. Bostwick DC; and Mann RB: Malignant‘lymphomas involving the prostate, Cancer 56: 2932 (1985). 16. King LS, and Cox TR: Lymphosarcoma of prostate, Am J Path01 27: 801 (1951). 17. Cartagena R, Baumgartner G, Wajsman Z, and Merrin C: Preliminary reticulum cell sarcoma of prostate gland, Urology 5: 815 (1975). 18. Gomez GA, et al: Primary chemotherapy for localized non-Hodgkin’s lymphoma of diffuse histology. Preliminary report of a prospective~study, Arch Intern Med 146: 1785 (1986). _ 19. Rosenbere SA. Diamond HD. laslowitz B. and Craver LF: Lymphosarcomg a review of 1,269 &es, Medicine 40: 31(1961). 20. Rudders RA, Ross ME, and DeLellis RA: Primary extranodal lymphoma: response to treatment and factors influencing prognosis, Cancer 42: 406 (1978). 21. Reddy S, Pellettiere E, Saxena V, and Hendrickson FR: Extranodal non-Hodgkin’s lymphoma, Cancer 46: 1925 (1980). 22. Narayana AS, Lo&ring S, and Weimar GW: Sarcoma of the bladder and nrostate. 1 Urol 119: 72 (1978). 23. Smith BH: and Del&er LP: Sarcoma of the prostate gland, Am J Clin Path01 58: 43 (1972). 24. Richmond J, Sherman RS, Diamond HD, and Craver LF: Renal lesions associated with malignant lymphomas, Am J Med 32: 184 (1962). 25. Fuller LM, et al: Extranodal lymphomas of the stomach and head and neck, in Ford RJ: Hodgkin’s Disease and NonHodgkin’s Lymphoma: New Perspectives in Immunopathology, Diagnosis, and Treatment, Houston, Raven Press, ~0127, 1984, p 341. 26. Dial DL: Lymphosarcoma of the prostate; report of a case, J Uro132: 79 (1934). 27. Mason DG: Primary malignant lymphocytoma of the prostate gland, Arch Path01 16: 803 (1933). 28. Humpel N, Richter-Levin D, and Gersh I: Primary lymphosarcoma of prostate, Urology 9: 461 (1977). 29. Sridhar KN, and Woodhouse CR: Prostatic infiltration in leukaemia and lymphoma, Eur Urol 9: 153 (1983). 30. Lewi HJE, et al: Urinary tract lymphomas, Br J Urol 58: 16 (1986).
UROLOGY
/ AUGUST
1988
i
VOLUME
XXXII,
NUMBER
2